CN115028522B - Preparation method of 2, 7-dihydroxy-9-fluorenone - Google Patents

Preparation method of 2, 7-dihydroxy-9-fluorenone Download PDF

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CN115028522B
CN115028522B CN202210897816.3A CN202210897816A CN115028522B CN 115028522 B CN115028522 B CN 115028522B CN 202210897816 A CN202210897816 A CN 202210897816A CN 115028522 B CN115028522 B CN 115028522B
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fluorene
diacyl
dibenzoate
dihydroxy
reaction
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CN115028522A (en
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郝卫
陈一贤
彭慧珍
冯冬祥
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Hangzhou Lupu Biotechnology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/04—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides onto unsaturated carbon-to-carbon bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/29—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of oxygen-containing functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes

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Abstract

The application relates to a preparation method of 2, 7-dihydroxyl-9-fluorenone, which comprises the following steps: (1) Mixing benzoic acid, an oxidant A, fluorene, a solvent A and a catalyst A for reaction to obtain 9H-fluorene-2, 7-diacyl dibenzoate; (2) Carrying out oxidation reaction on 9H-fluorene-2, 7-diacyl dibenzoate, a solvent B, a catalyst B and an oxidant B to obtain 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate; (3) Mixing 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate with a solvent C and alkali for hydrolysis reaction to obtain 2, 7-dihydroxy-9-fluorenone; the purity of the product is more than 99.5 percent, and the yield is more than 92 percent. The method has the advantages of good atom economy, environmental protection, simple preparation process, short synthetic route, high product purity, high yield and the like.

Description

Preparation method of 2, 7-dihydroxy-9-fluorenone
Technical Field
The application belongs to the technical field of organic synthesis and preparation of crude drug intermediates, and particularly relates to a preparation method of 2, 7-dihydroxy-9-fluorenone.
Background
2, 7-dihydroxy-9-fluorenone is an important organic synthetic raw material and can be used for preparing organic silicon polymer materials with fluorescence; can also be used for preparing fluorenyl polyether sulfone ketone thermoplastic resin; in addition, the product can be used as a key intermediate of tylulone (diethylamino-9-fluorenone) for synthesizing viral interferon and 2-hydroxyaminoacetyl-9-fluorenone for antispasmodic application. Therefore, the synthesis of 2, 7-dihydroxy-9-fluorenone has important research value.
The synthesis of 2, 7-dihydroxy-9-fluorenone was first reported by Krishna in 1967 (Journal of Medicinal Chemistry,1967, 10:99-101). Fluorene is used as a raw material, and 2, 7-dihydroxy-9-fluorenone is obtained through sulfonation, oxidization, alkali fusion and ring closure reaction. The method has the advantages of easily available raw materials and low cost. However, potassium permanganate is selected as an oxidant in the preparation process, a large amount of manganese dioxide solid waste is difficult to treat, the latter two steps of the reaction are high-temperature solid-phase reactions, the operation mode and the mass transfer process in the reaction process are difficult, and the requirements on reaction equipment are high and the reaction progress degree is not easy to control during production. The synthetic route is as follows:
in 1973, horner et al (Justus Liebigs Annalen der Chemie,1973,6 (5): 910-935.) reported the production of 4,4 '-dimethyl phenyl-2-carboxylic acid and 4,4' -dimethyl phenyl benzoic acid using methyl 2-bromo-5 methoxybenzoate and p-iodoanisole as starting materials under copper powder catalysis. 4,4' -dimethyl ether biphenyl-2-formic acid is closed loop under the action of polyphosphate, and methoxy is converted into hydroxyl by hydrobromic acid to obtain a target product. The method has mild conditions, but the raw materials are high in price, and the self-coupling product is provided in the first step, so that the yield is low. The synthetic route is as follows:
in 1976 Burke et al (Synthetic Communications,1976, 6:371-376) reported that fluorenone was used as the starting material, which was subjected to nitration, nitroreduction, diazotization, and substitution of hydroxyl groups for the diazotizationNitrogen group, 2, 7-dihydroxy-9-fluorenone is prepared. The method uses SnCl 2 The nitro group is reduced, and the cost is high. The synthetic route is as follows:
in 2004, epperson et al (Bioorganic)&medicinal chemistry,2004,12 (17): 4601-4611.) to report that methyl 2-bromo-5-hydroxybenzoate and 4-hydroxyphenylboronic acid are present in Pd 2 dba 3 And carrying out Suzuki coupling reaction under catalysis to obtain 4,4' -dihydroxybiphenyl-2-methyl formate, and then carrying out ring closure to obtain the target product. The reaction uses a homogeneous Pd catalyst, the price is high, and the price of the initial raw material is high, so that the catalyst is not suitable for industrial production. The synthetic route is as follows:
in 2008 Jeffrey et al (Journal of Materials Chemistry,2008,18 (28): 3361-3365.) reported that fluorenone was used as the starting material, acetic anhydride as the acylating agent, and anhydrous AlCl was used as the starting material 3 Under the catalysis of the catalyst, the Friedel-crafts acylation reaction is carried out, the product is subjected to Baeyer-Villiger oxidation rearrangement reaction in chloroform solvent by m-chloroperoxybenzoic acid (m-CPBA) and trifluoroacetic acid, the product is oxidized by sodium dichromate, and finally the target product is obtained by hydrolysis. The method has high cost, safety is required to be paid attention to when peroxide is used for production, and the sodium dichromate is difficult to post-treat. The synthetic route is as follows:
the prior art mainly has the following problems: 1) Due to the defects of high cost, dangerous operation, complexity, large solvent consumption and the like, satisfactory results are difficult to obtain in industrial preparation; 2) The method has the advantages of high raw material cost, low yield and difficult product purification, and particularly when potassium permanganate is selected as an oxidant for reaction in the preparation process of 2, 7-dipotassium sulfonate-9-fluorenone, a large amount of manganese dioxide solid waste is generated, and the manganese dioxide solid waste is difficult to treat; 3) The latter two steps of the reaction are high temperature solid phase reaction, the operation mode and the mass transfer process in the reaction process are difficult, the requirement on reaction equipment is high during production, and the reaction progress is not easy to control.
Disclosure of Invention
In order to overcome the defects and shortcomings of the prior art, the application provides a preparation method of 2, 7-dihydroxyl-9-fluorenone. The method for constructing 9H-fluorene-2, 7-diacyl dibenzoate by using a C-H living method and obtaining 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate by catalytic oxidation has the advantages of simple preparation process and short synthetic route.
In order to achieve the above purpose, the technical scheme adopted by the application is as follows:
a method for preparing 2, 7-dihydroxy-9-fluorenone, which comprises the following steps:
(1) Mixing benzoic acid, an oxidant A, fluorene, a solvent A and a catalyst A for reaction to obtain 9H-fluorene-2, 7-diacyl dibenzoate;
(2) Carrying out oxidation reaction on 9H-fluorene-2, 7-diacyl dibenzoate, a solvent B, a catalyst B and an oxidant B to obtain 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate; (3) Mixing 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate with a solvent C and alkali for hydrolysis reaction to obtain 2, 7-dihydroxy-9-fluorenone; the purity of the product is more than 99.5 percent, and the yield is more than 92 percent.
In the process of preparing 9H-fluorene-2, 7-diacyl dibenzoate, the application adopts a C-H activation method, adopts a metal catalysis method, avoids a method of using a sulfonated alkali fusion, and can be carried out without high temperature, wherein benzoyl groups are both arranged at the 2 position and the 7 position.
In the process of preparing 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate, the application adopts a catalytic oxidation method, the mass transfer process is better in homogeneous phase, the reaction selectivity is high, and the product can be obtained by only cooling, separating out and filtering after the reaction is finished and rinsing with water.
In the process of preparing 2, 7-dihydroxyl-9-fluorenone, the preparation method is hydrolyzed under the condition of catalytic amount of alkali, and the 2, 7-dihydroxyl-9-fluorenone can be directly obtained through acid regulation after the hydrolysis is finished. The purity of the 2, 7-dihydroxyl-9-fluorenone prepared by the method is more than 99.5%, and the yield is more than 92%.
Preferably, in the step (1), the oxidant a is one or more than two of sodium persulfate, potassium peroxymonosulfonate, silver oxide, iodobenzene diacetate and iodosobenzene; the solvent A is one or more than two of dichloroethane, chloroform, DMF, acetonitrile, dioxane, DMSO, toluene and chlorobenzene; the catalyst A is one or more than two of copper iodide, copper chloride, copper acetate, palladium chloride, palladium acetate, palladium nitrate and palladium bromide.
Preferably, the reaction temperature in the step (1) is 100-140 ℃ and the time is 5-30 h.
Preferably, in the step (1), the molar ratio of fluorene, benzoic acid, oxidant a and catalyst a is 1: 2-3: 2-3: 0.01 to 0.05; the mass ratio of the solvent A to fluorene is 5-10: 1.
preferably, in the step (2), the oxidant B is one or more than two of tert-butyl hydroperoxide, hydrogen peroxide, oxygen and peracetic acid; the solvent B is one or more than two of dichloroethane, chloroform, DMF, acetonitrile, dioxane, DMSO, toluene and chlorobenzene; the catalyst B is one or more than two of cuprous chloride, copper iodide, copper sulfate, copper acetate, potassium iodide and iodine.
Preferably, the reaction temperature in the step (2) is 20-80 ℃ and the time is 2-12 h.
Preferably, in the step (2), the mass ratio of the solvent B to the 9H-fluorene-2, 7-diacyl dibenzoate is 5-10: 1, the mole ratio of the oxidant B to the 9H-fluorene-2, 7-diacyl dibenzoate is 1-5: 1, the mass ratio of the catalyst B to the oxidant B is 0.05-0.3: 1.
preferably, in the step (3), the solvent C is one or more of ethanol, methanol, water, acetonitrile, dioxane, DMSO, toluene, chlorobenzene, or any combination of two or more thereof; the alkali is one or more than two of sodium hydroxide, potassium carbonate, sodium bicarbonate and sodium hydrogen.
Preferably, the reaction-temperature in step (3) is 80 to 100℃and the time is 5 to 10 hours.
Preferably, in the step (3), the mass ratio of the solvent C to the 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate is 5 to 10:1, wherein the molar ratio of the alkali to the 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate is 1-3: 1.
the reaction process of the application is as follows:
compared with the prior art, the application has the beneficial effects that:
1. the high-temperature solid-phase reaction is avoided, so that the operation mode and the mass transfer process in the reaction process are easier, and the industrialization is easier;
2. the method avoids the difficult removal of byproducts, greatly improves the yield, improves the yield by more than 10 percent compared with the traditional process, and obviously improves the purity of the product;
3. a large amount of solid waste is avoided, the environment is protected, and green chemistry is realized;
4. the preparation of 9H-fluorene-2, 7-diacyl dibenzoate is constructed by a C-H activation method, so that the atom economy is good.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of 2, 7-dihydroxy-9-fluorenone.
Detailed Description
The technical scheme of the present application is further specifically described by the following examples, which are given by way of illustration and not limitation. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
Example 1
A preparation method of 2, 7-dihydroxy-9-fluorenone, which comprises the following steps:
(1) Preparation of 9H-fluorene-2, 7-diacyl dibenzoate:
mixing benzoic acid, an oxidant A, fluorene, a solvent A and a catalyst A for reaction to obtain 9H-fluorene-2, 7-diacyl dibenzoate;
in the present application, the raw materials used are all conventional commercial products in the art or are prepared by conventional technical means in the art unless otherwise specified.
In the present application, the catalyst a includes one or more of copper iodide, copper chloride, copper acetate, palladium chloride, palladium acetate, palladium nitrate, and palladium bromide. In the present application, the solvent a is preferably toluene or xylene. In the present application, the molar ratio of fluorene to benzoic acid is preferably 1:2 to 3, more preferably 1:2.15. in the present application, the molar ratio of fluorene to iodosobenzene is preferably 1:2 to 3, more preferably 1:2.1. in the application, the mass ratio of the solvent A toluene to fluorene is preferably 5-10: 1, further preferably 7:1. in the application, the molar ratio of the palladium acetate to the fluorene in the catalyst A is preferably 0.01 to 0.05:1, further preferably 0.03:1.
in the present application, the temperature of the condensation reaction is preferably 100 to 140 ℃, and more preferably 110 to 130 ℃; the condensation reaction time is preferably 5 to 30 hours, more preferably 10 to 15 hours. The present application preferably fractionates out the water produced by the condensation reaction at the same time as the condensation reaction.
After the condensation reaction, the 9H-fluorene-2, 7-diacyl dibenzoate is preferably obtained by sequentially carrying out reduced pressure distillation, cooling, filtration and refining on the obtained condensation reaction product.
In the present application, the temperature of the reduced pressure distillation is preferably 70 to 90 ℃. In the present application, the cooling means is preferably ice water cooling. The refining mode is preferably to put the hydrolysate into methanol solution for heating and stirring washing. In the application, the mass ratio of the methanol to the wet weight of the hydrolysate is preferably 0.5-3: 1, more preferably 1.0 to 1.5:1. the refining temperature is preferably 40-50 ℃; the time for the purification is preferably 1 to 2 hours. The specific operation of the agitation washing is not particularly limited, and a refining method known to those skilled in the art may be employed. The application prepares the target product 9H-fluorene-2, 7-diacyl dibenzoate.
(2) Preparation of 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate:
the method comprises the steps of directly mixing the condensation reaction product with an oxidant B, a solvent B and a catalyst B for oxidation reaction to obtain 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate.
The condensation reaction product is directly mixed with the solvent B and the catalyst B, and then the oxidant B is dripped to carry out oxidation reaction. In the present application, the rate of the dropping is preferably 4 to 5mL/min. In the application, the oxidant comprises one or more of hydrogen peroxide, tert-butyl peroxide, peracetic acid and oxygen. In the present application, the solvent B is preferably one or more of dichloroethane, chloroform, DMF, acetonitrile, dioxane, DMSO, toluene, chlorobenzene. In the application, the catalyst B contains one or more of cuprous chloride, ketone iodide, copper sulfate, copper acetate, potassium iodide and iodine. In the application, the mass ratio of the solvent B dichloroethane to 9H-fluorene-2, 7-diacyl dibenzoate is preferably 5-10: 1, more preferably 6 to 7:1. in the present application, the molar ratio of the t-butyl peroxide to 9H-fluorene-2, 7-diacyl dibenzoate is preferably 1 to 5:1, further preferably 2.7:1. in the application, the mass ratio of the copper acetate to the tert-butyl peroxide is preferably 0.05-0.3: 1, further preferably 0.1:1.
in the present application, the temperature of the oxidation reaction is preferably 20 to 80 ℃, and more preferably 65 to 70 ℃; the reaction time is preferably 2 to 12 hours, more preferably 5 to 7 hours.
After the oxidation reaction, the obtained oxidation reaction product is sequentially cooled, filtered and refined to obtain the 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate.
In the present application, the cooling means is preferably normal temperature water cooling. In the present application, the refining is preferably carried out by stirring the oxidation product in an aqueous sodium dithionite solution. In the application, the mass ratio of the sodium dithionite to the wet weight of the oxidation product is preferably 0.1-1: 1, more preferably 0.2 to 0.3:1. in the present application, the mass ratio of the stirred water to the wet weight of the oxidation product is preferably 0.5 to 5:1, and more preferably 1.5:1, a step of; the temperature of the stirring and washing is preferably 20-40 ℃; the time for the recrystallization is preferably 1 to 2 hours. The specific operation of the agitation washing is not particularly limited, and a refining method known to those skilled in the art may be employed. The application adopts catalytic oxidation to prepare the key intermediate 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate.
(3) Preparation of 2, 7-dihydroxy-9-fluorenone:
under the protection of nitrogen, mixing the 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate, a solvent C and alkali for hydrolysis reaction, and regulating acid to obtain 2, 7-dihydroxy-9-fluorenone after the reaction is finished;
in the present application, the solvent includes one or more of ethanol, methanol, water, acetonitrile, dioxane, DMSO, toluene, chlorobenzene. In the present application, the alkali is preferably one or more of sodium hydroxide, potassium carbonate, sodium bicarbonate, and sodium hydrogen. In the present application, the mass ratio of the solvent water to the 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate is preferably 5 to 10:1, more preferably 6 to 7:1. in the present application, the molar ratio of the alkali sodium hydroxide to 9H-fluorene-2, 7-diacyl dibenzoate is preferably 1 to 3:1, further preferably 2.0:1.
after the hydrolysis reaction, the obtained hydrolysis reaction product is sequentially cooled, acid-regulated, filtered and refined to obtain the 2, 7-dihydroxy-9-fluorenone.
In the present application, the cooling means is preferably normal temperature water cooling. In the application, hydrochloric acid is used for acid regulation, and the molar ratio of hydrochloric acid to sodium hydroxide is preferably 1.5-3: 1, further preferably 2.1:1. the method of refining is preferably to put the hydrolysate into methanol solution and stir-wash. In the application, the mass ratio of the methanol to the wet weight of the hydrolysate is preferably 0.5-3: 1, more preferably 1.0 to 1.5:1. the refining temperature is preferably 10-20 ℃; the time for the purification is preferably 1 to 2 hours. The specific operation of the agitation washing is not particularly limited, and a refining method known to those skilled in the art may be employed. The application prepares the target product 2, 7-dihydroxyl-9-fluorenone by hydrolysis and acidification.
Example 2
(1) Synthesis of Compound 1:
50g of fluorene, 79g of benzoic acid, 124g of silver oxide, 2g of palladium acetate and 350g of toluene are added into a reaction vessel provided with a thermometer, a stirrer and a water separator, the reaction temperature is controlled to 115 ℃, water generated by the reaction is fractionated while the reaction is performed, the temperature is reduced to 70 ℃ after the reaction is performed for 10 to 15 hours, the filtration is performed while the reaction is still hot, the organic layer is decompressed and concentrated until a large amount of solid is separated out, 100g of methanol is added, the temperature is increased to 50 ℃, the mixture is stirred for 1 hour, the temperature is reduced to 10 ℃, the suction filtration is performed, and the 9H-fluorene-2, 7-diacyl dibenzoate methyl ester is obtained, the drying is performed at 105.3g at 70 ℃, and the yield is 85.4%.
(2) Synthesis of Compound 2:
to a reactor equipped with a thermometer, a stirrer, and a constant pressure dropper, 100g of methyl 9H-fluorene-2, 7-diacyldibenzoate, 8.2g of copper acetate, and 650g of dichloroethane were added. Slowly warm to 50℃and begin to slowly drop 118.6g of 70% t-butyl peroxide. After the dripping, the temperature is kept for 10 hours. After the reaction is finished, the temperature is reduced to 10 ℃, the wet product of the 9-oxo 9H-fluorene-2, 7-diacyl dibenzoate methyl is obtained by suction filtration, 115g of the wet product is stirred and washed for 1H by 20g of sodium dithionite and 115g of water, the refined product of the 9-oxo 9H-fluorene-2, 7-diacyl dibenzoate methyl is obtained by suction filtration, 96.8g of the wet product is obtained, and the yield is 94.0%.
(3) Synthesis of Compound 3:
to the reaction vessel, 700g of water, 60g of sodium carbonate and 100g of methyl 9-oxo 9H-fluorene-2, 7-diacyldibenzoate were added under nitrogen protection. Heating to 90 ℃ in nitrogen atmosphere, and preserving heat for 7h. After the reaction is finished, the temperature is reduced to 5 ℃, 47g of concentrated hydrochloric acid is slowly added into the reaction liquid in a dropwise manner, the temperature is kept at 5 ℃ for 1 hour after the completion of the dropwise addition, and the wet product of 2, 7-dihydroxy-9-fluorenone is obtained by suction filtration. The wet product is stirred and washed for 1h at 15-20 ℃ by 52g of methanol, the temperature is reduced to 5 ℃, the filtration is carried out, the 2, 7-dihydroxyl-9-fluorenone is obtained by drying, the purity of HPLC is 99.8%, and the yield is 94.2%. The hydrogen spectrum of the obtained product is shown in figure 1, 1 H NMR(500MHz,d 6 -DMSO)δ9.83(s,2H),7.36(d,J＝8.0Hz,2H),6.92–6.82(m,4H).
example 3
(1) Synthesis of Compound 1:
50g of fluorene, 79g of benzoic acid, 150g of sodium persulfate, 2g of palladium acetate and 350g of toluene are added into a reaction vessel provided with a thermometer, a stirrer and a water separator, the reaction temperature is controlled to 115 ℃, water generated by the reaction is fractionated while the reaction is performed, the temperature is reduced to 70 ℃ after the reaction is performed for 10 to 15 hours, the filtration is performed while the reaction is still hot, the organic layer is decompressed and concentrated until a large amount of solids are separated out, 100g of methanol is added, the temperature is increased to 50 ℃, the mixture is stirred for 1 hour, the temperature is reduced to 10 ℃, the suction filtration is performed, and the 9H-fluorene-2, 7-diacyl dibenzoate methyl ester is obtained, the temperature is dried to 103.1g at 70 ℃, and the yield is 84.2%.
(2) Synthesis of Compound 2:
to a reactor equipped with a thermometer, a stirrer, and a constant pressure dropper, 100g of methyl 9H-fluorene-2, 7-diacyldibenzoate, 7.0g of copper sulfate, and 650g of dichloroethane were added. Slowly warm to 50℃and begin to slowly drop 118.6g of 70% t-butyl peroxide. After the dripping, the temperature is kept for 14 hours. After the reaction is finished, the temperature is reduced to 10 ℃, and the wet product of 115g of 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate is obtained by suction filtration, 20g of sodium dithionite and 115g of water are used for stirring and washing the wet product for 1H, the refined product of 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate is obtained by suction filtration, 95.8g is obtained by suction filtration, and the yield is 93.0%.
(3) Synthesis of Compound 3:
700g of water, 19g of sodium hydroxide and 100g of methyl 9-oxo-9H-fluorene-2, 7-diacyldibenzoate were added to a reaction vessel under nitrogen protection. Heating to 90 ℃ in nitrogen atmosphere, and preserving heat for 7h. After the reaction is finished, the temperature is reduced to 5 ℃, 47g of concentrated hydrochloric acid is slowly added into the reaction liquid in a dropwise manner, the temperature is kept at 5 ℃ for 1 hour after the completion of the dropwise addition, and the wet product of 2, 7-dihydroxy-9-fluorenone is obtained by suction filtration. The wet product is stirred and washed for 1h at 15-20 ℃ by 52g of methanol, the temperature is reduced to 5 ℃, the suction filtration is carried out, and the wet product is dried to obtain 46.5g of 2, 7-dihydroxyl-9-fluorenone, the HPLC purity is 99.6%, and the yield is 93%.
Example 4
(1) Synthesis of Compound 1:
50g of fluorene, 79g of benzoic acid, 139g of iodized benzene, 2g of palladium acetate and 350g of toluene are added into a reaction vessel provided with a thermometer, a stirrer and a water separator, the reaction temperature is controlled to 115 ℃, water generated by the reaction is fractionated while the reaction is performed, the temperature is reduced to 70 ℃ after the reaction is performed for 10 to 15 hours, the filtration is performed while the reaction is still hot, the organic layer is decompressed and concentrated until a large amount of solids are separated out, 100g of methanol is added, the temperature is increased to 50 ℃, the mixture is stirred for 1 hour, the temperature is reduced to 10 ℃, the suction filtration is performed, and the 9H-fluorene-2, 7-diacyl dibenzoate methyl ester is obtained, the reaction temperature is dried to 101.2g at 70 ℃, and the yield is 82.7%.
(2) Synthesis of Compound 2:
to a reactor equipped with a thermometer, a stirrer, and a constant pressure dropper, 100g of methyl 9H-fluorene-2, 7-diacyldibenzoate, 3.0g of copper chloride, and 650g of dichloroethane were added. Slowly warm to 50℃and begin to slowly drop 118.6g of 70% t-butyl peroxide. After the dripping, the temperature is kept for 14 hours. After the reaction is finished, the temperature is reduced to 10 ℃, the wet product of the 9-oxo 9H-fluorene-2, 7-diacyl dibenzoate methyl is obtained by suction filtration, 115g of the wet product is stirred and washed for 1H by 20g of sodium dithionite and 115g of water, the refined product of the 9-oxo 9H-fluorene-2, 7-diacyl dibenzoate methyl is obtained by suction filtration, 95.7g of the wet product is obtained, and the yield is 92.9 percent.
(3) Synthesis of Compound 3:
to the reaction vessel, 700g of water, 69g of potassium carbonate and 100g of methyl 9-oxo 9H-fluorene-2, 7-diacyldibenzoate were added under nitrogen protection. Heating to 90 ℃ in nitrogen atmosphere, and preserving heat for 7h. After the reaction is finished, the temperature is reduced to 5 ℃, 47g of concentrated hydrochloric acid is slowly added into the reaction liquid in a dropwise manner, the temperature is kept at 5 ℃ for 1 hour after the completion of the dropwise addition, and the wet product of 2, 7-dihydroxy-9-fluorenone is obtained by suction filtration. The wet product is stirred and washed for 1h at 15-20 ℃ by 52g of methanol, the temperature is reduced to 5 ℃, the filtration is carried out, and the wet product is dried to obtain 46.3g of 2, 7-dihydroxyl-9-fluorenone with the yield of 92.6 percent.
The application has the advantages of simple preparation process, short synthetic route, easy industrialization realization, good atomic economy, environmental protection, high product purity, high yield and the like.
The application has been described in detail with reference to the examples, but the description is only specific embodiments of the application and should not be construed as limiting the scope of the application. It should be noted that, for those skilled in the art, it is intended that all changes and modifications made in the present application shall fall within the scope of the patent coverage of this application without departing from the spirit of the present application.

Claims (10)

1. A method for preparing 2, 7-dihydroxy-9-fluorenone, which is characterized by comprising the following steps:
(1) Mixing benzoic acid, an oxidant A, fluorene, a solvent A and a catalyst A for reaction to obtain 9H-fluorene-2, 7-diacyl dibenzoate;
(2) Carrying out oxidation reaction on 9H-fluorene-2, 7-diacyl dibenzoate, a solvent B, a catalyst B and an oxidant B to obtain 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate;
(3) Mixing 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate with a solvent C and alkali for hydrolysis reaction to obtain 2, 7-dihydroxy-9-fluorenone; the purity of the product is more than 99.5%, and the yield is more than 92%;
the oxidant A is one or more than two of sodium persulfate, potassium peroxomonosulphate, silver oxide, iodobenzene diacetate and iodoxybenzene; the catalyst A is one or more than two of palladium chloride, palladium acetate, palladium nitrate and palladium bromide;
the oxidant B is one or more than two of tert-butyl hydroperoxide, hydrogen peroxide, oxygen and peracetic acid; the catalyst B is one or more than two of copper chloride, copper iodide, copper sulfate and copper acetate.
2. The process for producing 2, 7-dihydroxy-9-fluorenone according to claim 1, wherein: in the step (1), the solvent A is one or more than two of dichloroethane, chloroform, DMF, acetonitrile, dioxane, DMSO, toluene and chlorobenzene.
3. A process for the preparation of 2, 7-dihydroxy-9-fluorenone according to claim 2, characterized in that: the reaction temperature in the step (1) is 100-140 ℃ and the reaction time is 5-30 h.
4. A process for the preparation of 2, 7-dihydroxy-9-fluorenone according to claim 2, characterized in that: in the step (1), the molar ratio of fluorene, benzoic acid, oxidant A and catalyst A is 1: 2-3: 2-3: 0.01 to 0.05; the mass ratio of the solvent A to fluorene is 5-10: 1.
5. the process for producing 2, 7-dihydroxy-9-fluorenone according to claim 1, wherein: in the step (2), the solvent B is one or more than two of dichloroethane, chloroform, DMF, acetonitrile, dioxane, DMSO, toluene and chlorobenzene.
6. The process for producing 2, 7-dihydroxy-9-fluorenone according to claim 5, wherein: the reaction temperature in the step (2) is 20-80 ℃ and the reaction time is 2-12 h.
7. The process for producing 2, 7-dihydroxy-9-fluorenone according to claim 5, wherein: in the step (2), the mass ratio of the solvent B to the 9H-fluorene-2, 7-diacyl dibenzoate is 5-10: the molar ratio of the oxidant B to the 9H-fluorene-2, 7-diacyl dibenzoate is 1-5: 1, the mass ratio of the catalyst B to the oxidant B is 0.05-0.3: 1.
8. the process for producing 2, 7-dihydroxy-9-fluorenone according to claim 1, wherein: in the step (3), the solvent C is one or more than two of ethanol, methanol, water, acetonitrile, dioxane, DMSO, toluene and chlorobenzene; the alkali is one or more than two of sodium hydroxide, potassium carbonate, sodium bicarbonate and sodium hydrogen.
9. The process for producing 2, 7-dihydroxy-9-fluorenone according to claim 8, wherein: the reaction temperature in the step (3) is 80-100 ℃ and the reaction time is 5-10 h.
10. The process for producing 2, 7-dihydroxy-9-fluorenone according to claim 8, wherein: in the step (3), the mass ratio of the solvent C to the 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate is 5-10: 1, wherein the molar ratio of the base to the 9-oxo-9H-fluorene-2, 7-diacyl dibenzoate is 1-3: 1.
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